PHILADELPHIA (November 28, 2018) – Warren D. Kruger, PhD, a professor at Fox Chase Cancer Center, has received a grant from the National Institutes of Health to study whether proteasome inhibitors (Pls) and proteostasis modulators are effective in restoring function to treating cystathionine beta synthase (CBS) deficiency, also known as classical homocystinuria.
CBS deficiency is a rare recessive genetic disorder that causes the accumulation of the toxic amino acid homocysteine in the blood. It is caused by mutations that alter the structure of the CBS protein, causing it to assume an incorrect 3D structure. Kruger is investigating if PIs, FDA approved drugs for the treatments of certain types of cancer, can be used to “coax” the misfolded proteins into the proper structure. This would represent a totally new use for this class of drugs.
“We are very excited by our initial findings, which show that we can restore substantial levels of CBS enzyme activity in mice expressing patient derived mutations by treating them with PI’s.” said Kruger.
If successful, the experiments described here could lead to novel treatments for CBS deficiency and potentially other genetic diseases associated with missense mutations.
The grant was awarded to Kruger in the amount of $1,372,500.